H2O2 modifies membrane structure and activity of acetylcholinesterase

The main factor of Alzheimer disease (AD) is beta-amyloid peptide (Abeta). It is known to affect acetylcholinesterase (AChE) through lipid peroxidation (LPO) initiated with H2O2 which is formed as a result of Abeta activity. The direct action of H2O2 on the enzyme is also possible. For membrane bound AChE of erythrocytes we observed inhibition under H2O2 action which was replaced by activation at small H2O2 concentrations. At higher substrate concentrations the inversion of the effect came at smaller concentrations of H2O2. For soluble erythrocytic AChE inhibition took place (caused by Km increase). Soluble enzyme from Electric Eel revealed inhibition, which was not replaced by activation at any concentration of peroxide. Low H2O2 concentrations caused intensification of lipid peroxidation in microsomes. The magnitude of the changes in LPO rate was within the range of the changes, where LPO system fulfills the control function for cell metabolism. With the help of ESR technique of spin probes it was found the rigidization under H2O2 action of close to surface area of lipid bilayer in erythrocytic and brain cell membranes. Summing up we can say that H2O2 modifies membrane structure and activity of AChE. Whether or not it will contribute to AD pathogenesis or is the manifestation of compensatory processes-the possible subject of discussion and further investigation.